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Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study

Kjeldsen, Sverre E.1,8; Kolloch, Rainer E.2; Leonetti, Gastone3; Malliond, Jean-Michel4; Zanchetti, Alberto5; Elmfeldt, Dag6; Warnold, Ingrid6; Hansson, Lennart7for the HOT Study Group

Original article

Objective We have assessed the influence of gender and age on the main outcome results of the Hypertension Optimal Treatment (HOT) study.

Design and interventions The aims of the HOT study were to study the relationship between three levels of target office diastolic blood pressure (BP) (≤ 90, ≤ 85 or ≤ 80 mmHg) and cardiovascular (CV) events in hypertensive patients, and to examine the effects of 75 mg acetylsalicylic acid (ASA) daily versus placebo.

Setting Outpatient clinical trial in 26 countries.

Patients A total of 18 790 patients (mean age 61.5 years, range 50–80) were randomized and followed for an average of 3.8 years until 71 051 patient-years and 683 events had occurred.

Main outcome measures CV death, myocardial infarction (MI) and stroke.

Results There were significantly fewer MIs in those in the lower diastolic BP target groups (3.0 versus 1.2 and 1.7 MIs/1000 patient-years, P for trend = 0.034) in women (n = 8883), whereas the similar but smaller trend (4.1 versus 4.1 and 3.4 MIs/1000 patient-years) was not statistically significant in men nor in the subgroup analysis of younger and older subjects. The effect of ASA on preventing MI was not influenced by age <65 years (P = 0.02) or age >65 years (P = 0.04) but was influenced by gender (P = 0.38 in women and P = 0.001 in men, lowered by 42% corresponding to a reduction from 5.0 to 2.9 MIs/1000 patient-years).

Conclusions The data of this HOT study sub-analysis suggest somewhat differentiated optimal gender- and age- dependent effects of anti-hypertensive and anti-platelet therapies; lowering of diastolic BP to about 80 mmHg in hypertensive women and, in addition, the administration of 75 mg of ASA to well-treated hypertensive men appear to effectively reduce the most common cardiovascular complication, i.e. myocardial infarction, in patients with essential hypertension.

1Department of Cardiology, Ullevaal University Hospital, Oslo, Norway

2Medizinische Klinik, Krankenanstalten Gilead, University of Münster, Bielefeld, Germany

3Divisione di Riabilitazione Cardiologica, Instituto Auxologico Italiano, Ospedale San Luca, Milan, Italy

4Medicine Interne et Cardiologie, Hôpital A Michallon, Universitaire de Grenoble, Grenoble, France

5Centro di Fisiologia Clinica e Ipertensione, University of Milan and Ospedale Maggiore, Milan, Italy

6HOT Coordinating Group, AstraZeneca, Mölndal, Sweden

7Department of Geriatrics, Clinical Hypertension Research, University of Uppsala, Uppsala, Sweden.

8Correspondence and requests for reprints to Sverre E. Kjeldsen MD PhD, Department of Cardiology, Ullevaal Hospital, N-0407 Oslo, Norway. Tel: +47 22 119101; fax: +47 22 119181; E-mail: or

Sponsorship: The principal sponsor of the HOT Study is Astra AB, Sweden. Local sponsors are Astra Merck Inc (USA), TEVA (Israel) and Hoechst (Argentina).

Received 11 November 1999 Revised 14 January 2000 Accepted 16 February 2000

© 2000 Lippincott Williams & Wilkins, Inc.